During pregnancy a variety of medical conditions require treatment with therapeutic agents. For instance, in Canada, excessive nausea and vomiting, possibly leading to hyperemesis gravidarum, are routinely treated with the prescription drug Diclectin® which contains a mixture in equal amounts of two active ingredients, namely pyridoxine HCl and doxylamine succinate.
Other conditions, pre-existing or developed during pregnancy, for example: diabetes, hypertension, blood cloths, depressive illness and heart disease are also commonly treated with prescription drugs.
In the case of pre-existing medical conditions numerous studies have shown that women have a tendency to abruptly stop taking their medications upon learning of the pregnancy, due to the perceived fear of birth defects1. In many cases, the risk to the health of the expectant mother and her baby is much higher if she stops or reduces her treatment than if she keeps taking the required medications.
Because of this perceived risk of harm to the fetus, otherwise known as the teratogenic risk, it is common for expectant mothers to discontinue taking a prescribed drug or to voluntarily diminish the prescribed dosage regimen. This often leads to dosage levels below therapeutic ranges in turn leading patients and the medical community to incorrectly conclude that a particular drug is clinically ineffective.
Discontinuing or altering drug therapy, often against competent medical prescription, may have grave consequences indeed. The health of the expectant mother and vicariously of the fetus may be put at great risk because of poor compliance with competent medical prescription. In many instances, the teratogenic risks must be weighed against the risk of catastrophic illness or worsening condition on the part of the expectant mother.
Even discounting the particular problem of patient compliance during pregnancy, drug therapy patient compliance is a widespread and difficult problem in the medical community. Non-compliance with prescribed drug dosage regimen is a huge health problem for patients in general. For example, it is estimated that less than 25% of outpatients will complete a 10 day course of antibiotic therapy for a strep throat or otitis media.
Matsui2 described that non-compliance with prescribed medication regimens may take many forms, including failure to fill the prescription, incorrect dosage, improper dosing interval, and premature discontinuation of the drug. Of course, the problem of non-compliance is magnified during pregnancy due to the importance of fetal safety.3 
Whenever women delay or discontinue use of medications during pregnancy due to fears related to fetal safety, the result may be a worsening of the condition and hospitalisation with use of multiple drug therapy. Furthermore, depending of the underlying condition, the worsening of the condition has serious consequences even including suicidal ideation. Einarson showed in her study1 on abrupt discontinuation of psychotropic drugs during pregnancy due to teratogenic fears, that 70.3% of women reported physical and psychological adverse effects to the point that 29.7% reported suicidal ideation (one third of them were hospitalised).
Despite these appalling statistics, the perception of the expectant mother remains shrouded by well-known errors of the past such as the widely publicized cases of thalidomide-induced fetal malformations. The graphic evidence of birth defects attributed to Thalidomide exposure during early pregnancy has left a teratogenicity stigma on all medications. Hence, it is commonly thought that all medications are to be avoided during pregnancy. In the study entitled “Prevention of Unnecessary Pregnancy Terminations by Counselling Women of Drug, Chemical, and Radiation Exposure During the First Trimester”, (1990)4, Koren showed that pregnant women exposed to drugs that are known to be non teratogenic, still perceive that their born-to-be baby has a 24% chance to suffer a major birth defect. This is about the same risk as an intra-uterine exposure to Thalidomide.
Scientific studies aimed at measuring the risk of drugs during pregnancy and patient education and counseling have so far been at the forefront of efforts to achieve better patient compliance with medical prescription.
However, even in the case of drugs having an extensively demonstrated record of fetal innocuousness, such as Diclectin® used to curb nausea and vomiting, the perception of latent risk remains. This perception of risk is of course carried over from the negative experiences of thalidomide which was also prescribed for nausea and vomiting during pregnancy and which was also provided as an oral dosage form. However, in reality, the active ingredient thalidomide and the active ingredients of Diclectin®, namely pyridoxine HCl and doxylamine succinate are completely unrelated. The risk perception carried-over from thalidomide is made apparent from patient compliance inquiries. Patient compliance with a medically prescribed dosage regimen of Diclectin® is clearly below what is recommend in the medical profession.
Even physicians and pharmacists are anxious about their liability associated with prescription or dispensing of medications to pregnant women. In the study by Pole5, it was shown that even health care professionals, after reading four different labels (all of them stating that drug is safe to be used in pregnancy), have evaluated these labels, as bearing a residual risk. They were unable to fully perceive or accept that medication is safe to be used in pregnancy. Patients, physicians and pharmacists are also worried about erroneous ingestion or dispensing of drugs not intended for use during pregnancy.
Despite the enormous volume of scientific evidence supporting Diclectin® harmlessness to the fetus, pregnant women persistently do not follow their physician's recommendation as to the adherence to Diclectin® dosage regimen. In most cases, women voluntarily reduce the dosage by half. In fact, they do not comply with the proper dosage regimen for Diclectin® to the point that some woman and some physicians believe that the medication is not effective. Therefore, non-compliance often results in a perception of product effectiveness failure.
Due to non-compliance with medical prescription, patients using less than prescribed amounts of Diclectin® will often find themselves in sub-therapeutic state. This prevents the medication from being effective and may aggravate the mother's condition to the point of developing hyperemesis gravidarum (HG). HG is the most severe end of nausea and vomiting during pregnancy, when a pregnant woman suffers from loss of more than 5% of her pre-pregnancy body weight, dehydration, acid-base disturbances, ketonuria and electrolyte imbalance. At this stage, physicians use intravenous medications that are often not recognised for safe use during pregnancy in order to control maternal condition. The use of these medications poses an unnecessary risk to the fetus. If this last resort medication appears to be ineffective due to the deterioration of the woman's condition, a therapeutic abortion may even be considered6.
In order to diminish potential for birth defects a vitamin intake is now medically recommended during pregnancy. For example, clinical evidence shows that taking folic acid before conception and during the first trimester of pregnancy may prevent up to 72% of the congenital abnormalities spina bifida and anencephaly7. Despite this, pregnant women are generally non compliant with recommended folic acid intake treatment thus putting an unborn child at an increased risk of major birth defect.
The situation is even worse if pregnant woman has been on a drug therapy that interferes with folic acid receptors (e.g., phenobarbital, phenytoin, carbamazepine, valproic acid). In this case, a pregnant woman is even at greater risk for having a baby with birth defect if she is not compliant.
Thus there remains an important need for innovative solutions to achieve better patient compliance of vitamins or drugs recommended for use during pregnancy.